ELMIRON

PENTOSAN POLYSULFATE SODIUM

ATC

Added

1 year ago on 19 December 2016

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PRECAUTIONS General ELMIRON® is a weak anticoagulant (1/15 the activity of heparin). At a daily dose of 300 mg (n = 128), rectal hemorrhage was reported as an adverse event in 6.3% of patients. Bleeding complications of ecchymosis, epistaxis, and gum hemorrhage have been reported (see ADVERSE REACTIONS ). Patients undergoing invasive procedures or having signs/symptoms of underlying coagulopathy or other increased risk of bleeding (due to other therapies such as coumarin anticoagulants, heparin, t-PA, streptokinase, high dose aspirin, or nonsteroidal anti-inflammatory drugs) should be evaluated for hemorrhage. Patients with diseases such as aneurysms, thrombocytopenia, hemophilia, gastrointestinal ulcerations, polyps, or diverticula should be carefully evaluated before starting ELMIRON®. A similar product that was given subcutaneously, sublingually, or intramuscularly (and not initially metabolized by the liver) is associated with delayed immunoallergic thrombocytopenia with symptoms of thrombosis and hemorrhage. Caution should be exercised when using ELMIRON® in patients who have a history of heparin induced thrombocytopenia. Alopecia is associated with pentosan polysulfate and with heparin products. In clinical trials of ELMIRON®, alopecia began within the first 4 weeks of treatment. Ninety-seven percent (97%) of the cases of alopecia reported were alopecia areata, limited to a single area on the scalp. Hepatic Insufficiency ELMIRON® has not been studied in patients with hepatic insufficiency. Because there is evidence of hepatic contribution to the elimination of ELMIRON®, hepatic impairment may have an impact on the pharmacokinetics of ELMIRON®. Caution should be exercised when using ELMIRON® in this patient population. Mildly (< 2.5 × normal) elevated transaminase, alkaline phosphatase, γ-glutamyl transpeptidase, and lactic dehydrogenase occurred in 1.2% of patients. The increases usually appeared 3 to 12 months after the start of ELMIRON® therapy, and were not associated with jaundice or other clinical signs or symptoms. These abnormalities are usually transient, may remain essentially unchanged, or may rarely progress with continued use. Increases in PTT and PT (< 1% for both) or thrombocytopenia (0.2%) were noted. Information for Patients Patients should take the drug as prescribed, in the dosage prescribed, and no more frequently than prescribed. Patients should be reminded that ELMIRON® has a weak anticoagulant effect. This effect may increase bleeding times. Laboratory Test Findings Pentosan polysulfate sodium did not affect prothrombin time (PT) or partial thromboplastin time (PTT) up to 1200 mg per day in 24 healthy male subjects treated for 8 days. Pentosan polysulfate sodium also inhibits the generation of factor Xa in plasma and inhibits thrombin-induced platelet aggregation in human platelet rich plasma ex vivo. (See PRECAUTIONS-Hepatic Insufficiency Section for additional information.) Carcinogenicity, Mutagenesis, Impairment of Fertility Long term carcinogenicity studies of ELMIRON® in F344/N rats and B6C3F1 mice have been conducted. In these studies, ELMIRON® was orally administered once daily via gavage, 5 days per week, for up to 2 years. The dosages administered to mice were 56, 168 or 504 mg/kg. The dosages administered to rats were 14, 42, or 126 mg/kg for males, and 28, 84, or 252 mg/kg for females. The dosages tested were up to 60 times the maximum recommended human dose (MRHD) in rats, and up to 117 times the MRHD in mice, on a mg/kg basis. The results of these studies in rodents showed no clear evidence of drug-related tumorigenesis or carcinogenic risk. Pentosan polysulfate sodium was not clastogenic or mutagenic when tested in the mouse micronucleus test or the Ames test (S. typhimurium). The effect of pentosan polysulfate sodium on spermatogenesis has not been investigated. Pregnancy Category B Reproduction studies have been performed in mice and rats with intravenous daily doses of 15 mg/kg, and in rabbits with 7.5 mg/kg. These doses are 0.42 and 0.14 times the daily oral human doses of ELMIRON® when normalized to body surface area. These studies did not reveal evidence of impaired fertility or harm to the fetus from ELMIRON®. Direct in vitro bathing of cultured mouse embryos with pentosan polysulfate sodium (PPS) at a concentration of 1 mg/mL may cause reversible limb bud abnormalities. Adequate and well-controlled studies have not been performed in pregnant women. Because animal studies are not always predictive of human response, this drug should be used in pregnancy only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ELMIRON® is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients below the age of 16 years have not been established.

Usage information

DOSAGE AND ADMINISTRATION The recommended dose of ELMIRON® is 300 mg/day taken as one 100 mg capsule orally three times daily. The capsules should be taken with water at least 1 hour before meals or 2 hours after meals. Patients receiving ELMIRON® should be reassessed after 3 months. If improvement has not occurred and if limiting adverse events are not present, ELMIRON® may be continued for another 3 months. The clinical value and risks of continued treatment in patients whose pain has not improved by 6 months is not known.

Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ELMIRON® is administered to a nursing woman.

Interactions

Drug-Drug Interactions In a study in which healthy subjects received pentosan polysulfate sodium 100 mg capsule or placebo every 8 hours for 7 days, and were titrated with warfarin to an INR of 1.4 to 1.8, the pharmacokinetic parameters of R-warfarin and S-warfarin were similar in the absence and presence of pentosan polysulfate sodium. INR for warfarin + placebo and warfarin + pentosan polysulfate sodium were comparable. See also PRECAUTIONS on the use of ELMIRON® in patients receiving other therapies with anticoagulant effects.

More information

Category

Value

Authorisation number

NDA020193

Agency product number

914032762Y

Orphan designation

No

Product NDC

55154-0553

Date Last Revised

14-12-2017

Type

HUMAN PRESCRIPTION DRUG

RXCUI

199498

Storage and handling

Storage Store at controlled room temperature 15°–30°C (59°–86°F).

Marketing authorisation holder

Cardinal Health

Warnings

What is the most important information I should know about ELMIRON®? ELMIRON® (pronounced EL ma ron) is used to treat the pain or discomfort of interstitial cystitis (IC). You must take ELMIRON® as prescribed by your doctor in the dosage prescribed but no more frequently than prescribed. ELMIRON® is a weak anticoagulant (blood thinner) which may increase bleeding. Call your doctor if you will be undergoing surgery or will begin taking anticoagulant therapy such as warfarin sodium, heparin, high doses of aspirin, or anti-inflammatory drugs such as ibuprofen.